Avaliação da toxicidade e das atividades anti-inflamatória e analgésica do extrato etanólico de Gomphrena celosioides Mart. (Amaranthaceae) em roedores

Abstract

Introduction: Gomphrena celosioides, is popularly known in Brazil as “Perpétua Brava” and used for the treatment of several diseases: liver, dermatological, dysmenorrhea, infections, pain, among others. Chemical study of the ethanolic extract of the leaves showed the presence of malic acid, caffeic acid, ferulic acid, catechin, vanillic acid, irisone B, dimethoxyflavone, caffeyl-glucose, the biological activities of the plant have already been described as anti-inflammatory, diuretic, antimicrobial, gastroprotection, antioxidant and immunomodulators. In this context, the objective of the research was to evaluate the anti-inflammatory, anti arthritic, analgesic and toxicological potential of the ethanolic extract of Gomphrena celosioides (EEGC). Materials and Method: Paw edema, mechanical hyperalgesia and cold allodine were induced in male Swiss mice with carrageenan after oral treatment of EEGC at doses of 300, 700 and 1000 mg/kg, control and 1 mg/kg dexamethasone. The female Swiss mouse pleurisy model was induced after administration of 1 mL of intrapleural carrageenan and the animals treated with EEGC at doses of 300, 700 and 1000 mg/kg, control and dexamethasone (1 mg/kg). For arthritis induction, C57Bl6 mice were induced with intra-articular zymosan and after 30 minutes treated with EEGC 300 mg / kg, control and dexamethasone 1 (mg/kg). For the evaluation of peritonitis, male Swiss mice were divided into a naive group, control, EEGC 300 mg/kg and dexamethasone (1 mg/kg). 30 minutes after treatment, peritonitis was induced by zymosan. Leukocyte rolling and adhesion in mesenteric endothelium was evaluated after carrageenan induction and treatment with EEGC 300 mg/kg and Indomethacin (5 mg/kg). The persistent model for anti-inflammatory and analgesic evaluation was performed with Freund's Complete Adjuvant (CFA) in C57BL6 mice treated with EEGC 100 mg/kg, saline control and dexamethasone 1 mg/kg for 22 days. The toxicological evaluation was determined by an acute model using Wistar rats following OECD 2008a guideline and subacute was performed with Swiss mice evaluated for 28 days, evaluating hypocratic, behavioral, histological, biochemical and hematological parameters. Results: EEGC showed a reduction in Paw Edema in all doses in the 3 hours evaluated, it was still possible to observe a reduction in mechanical hyperalgesia in the third hour in all evaluated doses and a reduction in cold allodine with 3 hours in the dose of 700 mg / kg and with 4 hours in 700 and 1000 mg/kg in a model induced by carrageenan. After induction of pleurisy, it was possible to observe a reduction in leukocyte migration at doses of 700 and 1000 mg/kg, but there was no reduction in protein leakage in the pleural cavity. A reduction in leukocyte migration and mechanical hyperalgesia was observed in a model of arthritis induced by Zymosan after treatment with EEGC 300 mg/kg. EEGC also reduced leukocyte migration in Zymosan-induced peritonitis at a dose of 300 mg/kg, but there was no difference in the nitric oxide (NO) dosage. After assessing the reduction of leukocytes in the peritoneal cavity, the leukocyte rolling and adhesion in mesenteric endothelium was evaluated and a reduction in both rolling and adhesion was observed after induction with carrageenan and treatment with 300 mg/kg EEGC. In a persistent CFA model, animals treated with EEGC 100 mg/kg reduced paw edema on the 22nd day, cold allodynia on 6, 11 and 16 days and reduced mechanical hyperalgesia on all evaluated days. The acute toxicological analysis after administration of 2000 mg/kg in Wistar rats, there was no change in the parameters evaluated as well as no changes in the parameters evaluated for subacute toxicity at doses of 75, 150 and 300 mg / kg. Conclusion: EEGC demonstrated anti-inflammatory, antiarthritic and analgesic potential in different models of acute and persistent induction, with decreased bearing and leukocyte endothelial adhesion. Still, it did not present toxicity in an acute and sub-acute evaluation model.